Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects / 生物医学与环境科学（英文）

OBJECTIVE@#The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker.@*METHODS@#A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL).@*RESULTS@#The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m 3. The OELs for COEs exposure using the BBMD were 0.00170 mg/m 3 for the total population, 0.00158 mg/m 3 for males, and 0.00174 mg/m 3 for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m 3, respectively.@*CONCLUSION@#Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m 3. This value will provide a benchmark for determining possible OELs.

Thoracoscopic laparoscopy-assisted Ivor-Lewis resection of esophagogastric junction cancer / 中华肿瘤杂志

Objective: To investigate the outcome of patients with esophagogastric junction cancer undergoing thoracoscopic laparoscopy-assisted Ivor-Lewis resection. Methods: Eighty-four patients who were diagnosed with esophagogastric junction cancer and underwent Ivor-Lewis resection assisted by thoracoscopic laparoscopy at the National Cancer Center from October 2019 to April 2022 were collected. The neoadjuvant treatment mode, surgical safety and clinicopathological characteristics were analyzed. Results: Siewert type Ⅱ (92.8%) and adenocarcinoma (95.2%) were predominant in the cases. A total of 2 774 lymph nodes were dissected in 84 patients. The average number was 33 per case, and the median was 31. Lymph node metastasis was found in 45 patients, and the lymph node metastasis rate was 53.6% (45/84). The total number of lymph node metastasis was 294, and the degree of lymph node metastasis was 10.6%(294/2 774). Among them, abdominal lymph nodes (100%, 45/45) were more likely to metastasize than thoracic lymph nodes (13.3%, 6/45). Sixty-eight patients received neoadjuvant therapy before surgery, and nine patients achieved pathological complete remission (pCR) (13.2%, 9/68). Eighty-three patients had negative surgical margins and underwent R0 resection (98.8%, 83/84). One patient, the intraoperative frozen pathology suggested resection margin was negative, while vascular tumor thrombus was seen on the postoperative pathological margin, R1 resection was performed (1.2%, 1/84). The average operation time of the 84 patients was 234.5 (199.3, 275.0) minutes, and the intraoperative blood loss was 90 (80, 100) ml. One case of intraoperative blood transfusion, one case of postoperative transfer to ICU ward, two cases of postoperative anastomotic leakage, one case of pleural effusion requiring catheter drainage, one case of small intestinal hernia with 12mm poke hole, no postoperative intestinal obstruction, chyle leakage and other complications were observed. The number of deaths within 30 days after surgery was 0. Number of lymph nodes dissection, operation duration, and intraoperative blood loss were not related to whether neoadjuvant therapy was performed (P>0.05). Preoperative neoadjuvant chemotherapy combined with radiotherapy or immunotherapy was not related to whether postoperative pathology achieved pCR (P>0.05). Conclusion: Laparoscopic-assisted Ivor-Lewis surgery for esophagogastric junction cancer has a low incidence of intraoperative and postoperative complications, high safety, wide range of lymph node dissection, and sufficient margin length, which is worthy of clinical promotion.

Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Survival analysis of patients with acute aortic dissection with different treatment modalities / 中国医师杂志

Objective:To investigate the survival status of patients with acute aortic dissection (AD) treated by different methods, and evaluate the factors affecting the survival of AD patients.Methods:According to the retrospective research method, the patients diagnosed with AD in the Affiliated Hospital of Jining Medical University from January 1, 2019 to December 31, 2020 were collected. The treatment data and follow-up of patients were counted, the survival of patients was analyzed by Kaplan-Meier survival curve, and the factors affecting the survival of patients were analyzed by Cox regression model.Results:A total of 251 patients were included in this study, including 169 patients in the surgical treatment group and 82 patients in the conservative treatment group. The in-hospital fatality rate in the surgical treatment group and the conservative treatment group were 8.88%(15/169) and 43.90%(36/82), respectively, and the difference were statistically significant ( P<0.05). The survival time of surgical treatment group and conservative treatment group was (328.08±8.17)d and (194.43±19.80)d, respectively, and the difference was statistically significant ( P<0.05). Surgery ( RR=5.424, 95% CI: 2.821-10.428, P<0.05), acute myocardial infarction ( RR=0.448, 95% CI: 0.221-0.906, P<0.05), and shock ( RR=0.266, 95% CI: 0.102-0.693, P<0.05) and stroke ( RR=0.277, 95% CI: 0.127-0.604, P<0.05) were the factors affecting 1-year survival in AD patients. Conclusions:Active surgical treatment is recommended for AD patients with surgical indication as soon as possible.

Establishment of HPLC fingerprint and content determination of 8 components in Jianpi huayu decoction / 中国药房

OBJECTIVE To establish the HPLC fingerprint of Jianpi huayu decoction， and to determine the contents of 8 components. METHODS Thermo Hypersil Gold C18 column was used with mobile phase consisted of methanol-0.05% phosphoric acid aqueous solution （gradient elution） at the flow rate of 1.0 mL/min. The column temperature was 30 ℃， the injection volume was 5 μL. The detection wavelength of matrine was 211 nm， and the other components’ detection wavelength was 283 nm. The similarity evaluation of HPLC fingerprints for 10 batches of Jianpi huayu decoction was performed by using the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. The contents of chlorogenic acid， vanillic acid， p-coumaric acid， ferulic acid， hesperidin， quercetin， bergapten and matrine in the samples were determined by HPLC. RESULTS HPLC fingerprint of Jianpi huayu decoction was established. A total of 27 common peaks were identified， and 8 components were identified. The similarity between 10 batches of samples and the control map ranged from 0.942-0.999. RSDs of precision， repeatability and stability tests were less than 3% （n＝6）. The average recoveries of chlorogenic acid， vanillic acid， p-coumaric acid， ferulic acid， hesperidin， quercetin， bergapten and matrine were 99.48%， 101.32%， 101.18%， 100.79%， 101.12%， 99.19%， 99.81% and 102.46%， respectively； RSDs were 1.34%， 0.93%， 1.90%， 1.84%， 0.54%， 1.53%， 1.33% and 1.01%， respectively （n＝6）. The contents were 0.021-0.061， 0.025-0.034， 0.116-0.295， 0.006- 0.062， 0.014-0.053， 0.017-0.026， 0.014-0.027 and 14.05-24.11 mg/g， respectively. CONCLUSIONS The established fingerprint and content determination method can provide a reference for the quality control and subsequent preparation development for Jianpi huayu decoction.

Study on release and antioxidant activity of quercetin after loaded by hot alkali hydrolysis modified UiO-66 material / 药学学报

UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.

Micropulse laser combined with intravitreal injection of Ranibizumab in the treatment of macular edema secondary to non-ischemic branch retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of micropulse laser combined with intravitreal injection of ranibizumab in the treatment of macular edema(ME)secondary to non-ischemic branch retinal vein occlusion(BRVO).METHODS: A total of 200 cases(200 eyes)of non-ischemic BRVO secondary to ME who were treated in our hospital from January 2020 to March 2022 were selected and divided into the control group(100 cases, 100 eyes)and the observation group(100 cases, 100 eyes)by random number table. The control group was given intravitreal injection of ranibizumab, and the observation group was given micropulse laser combined with intravitreal injection of ranibizumab. The best corrected visual acuity(BCVA), central macular thickness(CMT), subfoveal choroidal thickness(SFCT), total number of injections, macular leakage and complications were compared between two groups.RESULTS: After treatment, the BCVA of the two groups were improved, and the BCVA of the observation group was better than those in the control group at 1, 3, 6 and 12mo after treatment(all P&#x0026;#x003C;0.05). After treatment, the CMT and SFCT of the two groups decreased, and the CMT and SFCT of the observation group was lower than those in the control group at 1, 3, 6 and 12mo after treatment(all P&#x0026;#x003C;0.05). The total number of injections in the observation group during the treatment period was less than that in the control group [(4.06±1.12)times vs.(5.32±1.15)times](t=5.852, P&#x0026;#x003C;0.001). The leakage rates of the control group and the observation group after 12mo of treatment were 69.0% and 27.0% respectively, with statistical significance between the two groups(χ2=35.337, P&#x0026;#x003C;0.001). The incidence of complications in the control group and observation group were 11.0% and 5.0% respectively, with no statistical significance between the two groups(χ2=2.446, P=0.118).CONCLUSION: Micropulse laser combined with intravitreal injection of ranibizumab has a significant clinical efficacy in the treatment of ME secondary to non-ischemic BRVO, which is safe and can improve patients' vision and ME, reduce the total doses of ranibizumab without increasing the incidence of complications.

Assessment of adequacy of colonoscopic bowel preparation based on nomogram visualization / 中华消化内镜杂志

Objective:To establish a nomogram to evaluate the adequacy of bowel preparation before colonoscopy and to guide clinical decision-making.Methods:A total of 1 023 valid questionnaires from subjects who underwent diagnosis and treatment of colonoscopy at the digestive endoscopy center, Xiangya Hospital, Central South University from September 2020 to March 2021 were finally returned. The contents of the questionnaire mainly included the clinical characteristics, defecation habits, the number of defecation and the time of the last defecation after taking the medicine and the self-assessment results of bowel preparation before colonoscopy. Subjects' bowel preparation was graded with the Boston bowel preparation scale (BBPS) by a designated endoscopist in a single blinded method. Multivariate analyse was used to explore the influencing factors for bowel preparation adequacy, and a nomogram was drawn accordingly.Results:Based on BBPS scores, bowel preparation of 674 subjects were adequate and 349 were inadequate. Multivariate analyse identified the number of defecation per week ( OR=1.649,95% CI:1.233-2.204, P=0.001), the number of defecation after medication ( OR=3.963, 95% CI: 1.851-8.485, P<0.001), the time of the last defecation after medication ( OR=5.151, 95% CI: 1.152-23.037, P=0.032), and self-assessment of bowel preparation before examination ( OR=8.284, 95% CI: 2.042-33.601, P=0.003) were influencing factors for the adequacy of bowel preparation for colonoscopy. The area under the receiver operating characteristic curve of assessment of colonoscopic bowel preparation adequacy with nomogram visualization according to influencing factors was 0.913, optimal cutoff value was 0.824, the sensitivity was 0.746, and the specificity was 0.971 under the internal validation cohort. Conclusion:The nomogram based on the number of defecation per week, the number of defecation after medication, the time of the last defecation after medication, and self-assessment of bowel preparation before examination could evaluate the adequacy of bowel preparation before colonoscopy, which is worthy of application.

The significance of tumor deposits in prognosis and lymph node staging in gastric cancer patients / 中华普通外科杂志

Objective:To investigate the effect of tumor deposits on the prognosis and lymph node staging in patients with gastric cancer.Methods:The clinicopathological data of 907 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from Jan to Dec 2016 were retrospectively analyzed. According to the pathological diagnosis, the patients were divided into tumor deposits positive group (121 cases) and tumor deposits negative group (786 cases), and the relationship between tumor deposits and clinicopathological features and prognosis was analyzed.Results:Tumor deposits were found in 121 patients among 907 cases. Univariate analysis showed that tumor deposits were correlated with pT stage, pN stage, pTNM stage, tumor diameter, nerve invasion and vascular invasion (all P<0.05). Multivariate analysis showed that pT stage ( P<0.001), pN stage ( P=0.002), pTNM stage ( P=0.001), tumor diameter ( P=0.033),nerve invasion ( P=0.017), vascular invasion ( P=0.011) were the independent influencing factors of positive tumor deposits. The prognosis of patients with tumor deposits was worse than those without ( χ2=77.869, P<0.001). By univariate analysis, age, tumor location, size, pT stage, pN stage, pTNM stage, tumor thrombus, nerve invasion, tumor deposits and number affected prognosis (all P<0.05). Multivariate analysis showed that age, pT stage, pN stage, pTNM stage, nerve invasion, vascular invasion and the number of tumor deposits were independent prognostic factors (all P<0.05). By stratified analysis tumor deposits were found to have statistical difference in N0~N3a stage (all P<0.05). Conclusion:Tumor deposits is an independent risk factor affecting the prognosis of gastric cancer patients.

Clinical analysis of cervical lesions in 1 337 postmenopausal women diagnosed during screening / 中华老年医学杂志

Objective:To screen and diagnose cervical lesions in middle-aged and elderly postmenopausal women and analyze the characteristics of cervical lesions in middle-aged and elderly women.Methods:A retrospective analysis was conducted on the screening data of 1 337 postmenopausal women aged between 50 and 86 years who visited the outpatient clinics of the gynecology department of Beijing Hospital between January, 2015 and December, 2019.Participants were divided into groups based on age, with 787 in the 50-59 years old group, 483 in the 60-69 years old group, 60 in the 70-79 years old group, and 7 in the 80-89 years old group.Exfoliated cervical cells were collected, and high-risk human papillomavirus(HPV)detection and liquid-based cervical cytology examination were performed to confirm the diagnosis based on the pathological results of cervical biopsy.Cervical lesions were analyzed.Results:53.0%(708)of the 1 337 enrolled patients made their hospital visits because of symptoms.There were 666 patients(49.8%)with cervical lesions, including 357 with low-grade squamous intraepithelial lesions(LSIL), 252 with high-grade squamous intraepithelial lesions(HSIL)and 57(4.3%)with cervical cancer.The 70-79 group showed the highest incidence of HSIL at 30.0%(18/60), while the 50~59 group had the highest incidence of LSIL at 30.6%(241/787), and there were significant differences in different types of cervical lesions between different age groups( χ2=28.919, P<0.01). Liquid-based cervical cytology examination revealed a positive rate of 51.6%(166/322)for LSIL, a positive rate of 70.8%(143/202)for HSIL, and a rate of 71.4%(25/35)for cervical cancer.There were significant differences in LSIL, HSIL and other above-mentioned positive rates of lesions( P<0.05). In the cervical malignancy group, cytological high-grade squamous epithelial lesions made up 51.4%(18/35). Intraepithelial lesions or cancerous lesions represented 29.2%(59/202)in the HSIL group.The rate of intraepithelial lesions or cancerous lesions in the LSIL group was 48.4%(156/322), with statistically significance in these differences( χ2=118.806, P<0.01). Chronic cervicitis was found in 52.9%(109)of 206 patients with atypical squamous cells and positive HPV, and in 76.2%(16)of 21 patients without HPV.HPV examination was completed in 1 301 patients, with 69.4%(903)having infections by one HPV strain and 30.6%(398)having infections by mixed HPV strains.Biopsy results showed that the rates of HPV infections in LSIL, HSIL and cancer patients were 84.6%(302/357), 95.9(185/193)and 100%(54/54), respectively, and the differences in these pathological results were statistically significant( P<0.01). HPV16 was the most common subtype in single HPV strain infections.The most common subtypes of HPV infections in cervical lesions with HSIL and above were HPV16 and HPV18.The agreement rate was 52.4%(187/357)for LSIL, 60.7%(153/252)for HSIL, and 64.9%(37/57)for cervical cancer between diagnoses based on cervical biopsy and those based on colposcopy.As the severity of lesions increased, the accuracy of colposcopy also increased.Differences between colposcopic diagnosis and pathological diagnosis on different types of cervical lesions were statistically significant( χ2=550.382, P<0.01).1 310 patients underwent endocervical curettage, identifying 120 cases of HSIL and 39 cases of cervical cancer, with a detection rate of 55.8%(159/285). Conclusions:The incidence of cervical cancer is high in elderly women.The incidences of high-grade lesions and cervical cancer in patients with atypical squamous cells plus HPV infections in the cervix are also high.Postmenopausal patients with cervical lesions are mainly infected by a single HPV subtype, with subtype 16 being the most common one.With increasing severity of lesions, the accuracy of colposcopy-based diagnosis increases and the rate of missed diagnosis decreases.Cervical curettage is an important means to reduce missed diagnosis with colposcopy.

Evaluation of application effect of two-way referral service in the referral and treatment of coronary disease / 中华健康管理学杂志

Objective:To evaluate the effect of two-way referral service in referral and treatment of patients with coronary disease.Methods:A non-randomized controlled study was used, 80 patients with coronary disease who were referred to the First Affiliated Hospital of Xinjiang Medical University through the fast referral channel, also called green referral channel (GRC) of telemedicine service mode from January 2021 to January 2022 were selected as the GRC referral group. A propensity score was used to match 110 patients from the same period with coronary disease who were referred to this hospital through conventional medical channels and had similar basic conditions such as age, gender, region and medical insurance type as the conventional referral group. The differences in disease severity, referral time, hospitalization cost and other indicators were compared using t-test, χ2 test and nonparametric test between the two groups, and the satisfaction of the GRC referral group was investigated. Results:The proportion of patients with heart function grade Ⅲ (NYHA grading), heart failure, atrial fibrillation and interventional therapy in the GRC referral group was significantly higher than conventional referral group (all P<0.05). The total referral time and bed waiting time of patients in the GRC referral group were significantly shorter than conventional referral group [14.16 (9.62, 25.61) vs 34.39 (28.51, 49.68) h, 2.13 (0.83, 6.64) vs 24.58 (20.27, 27.68) h] ( Z=8.465, 9.172, all P<0.001). The hospitalization cost, surgical treatment cost and material cost in GRC referral group were significantly higher than conventional referral group [24 755 (11 559, 56 521) vs 14 700 (9 375, 29 534) CNY, 6 013 (2 096, 8 256) vs 2 562 (2 044, 6 154) CNY, 12 093 (1 267, 35 689) vs 1 329 (826, 16 125) CNY] ( Z=2.814, 2.917, 3.353, all P<0.05), and the diagnosis cost was significantly lower than conventional referral group [4 878 (3 628, 6 847) vs 5 719 (4 228, 7 639) CNY] ( Z=2.323, P<0.05). In the GRC referral group, the satisfaction rates with referral process, visit time and patient experience were all above 90%. Conclusion:Two-way referral service based on telemedicine has a good application effect in the referral and treatment of patients with coronary disease.

Effect of preoperative TACE on the complications after hepatectomy for hepatocellular carcinoma: a propensity score matching analysis / 中华肝胆外科杂志

Objective:To study the effect of preoperative transcatheter arterial chemoembolization (TACE) on postoperative complications after hepatectomy in patients with hepatocellular carcinoma (HCC) by propensity score matching analysis.Methods:Of 1 666 patients with HCC undergoing hepatectomy in Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology and Tianyou Hospital of Wuhan University of Science and Technology from March 2015 to March 2021 were retrospectively screened. Of 262 patients were enrolled, including 236 males and 26 females, aged (50.3±11.8) years. Of 131 patients were enrolled in both the single surgery group and the combined group (preoperative TACE + surgical resection). Factors affecting the complications after hepatectomy in patients with HCC were analyzed using univariate and multivariate logistic regression method.Results:After matching the propensity score, the incidence of postoperative complications in the single surgery group was 22.1% (29/131), lower than that in the combined group [41.2% (54/131), χ 2=11.02, P<0.001]. The incidence of bile leakage in the single surgery group [2.3% (3/131)] was also lower than that in the combined group [(9.2% (12/131), χ 2=5.73, P=0.017]. Multivariate logistic regression analysis showed that the combined group ( OR=2.43, 95% CI: 1.28-4.61, P=0.007) had an increased incidence of postoperative complications, so did patients with a preoperative alpha-fetoprotein > 400 μg/L, anatomic hepatectomy, long operation time, and hilar occlusion. Conclusion:Preoperative TACE could be a risk factor for postoperative complications in patients with HCC, especially for the postoperative biliary leakage.

Flavonoid glycosides from the water extract of Artemisia annua L / 药学学报

Twenty one flavonoid glycosides were isolated and purified from n-butanol portion of the water extract of A. annua by various chromatographic techniques such as HP-20 macroporous adsorption resin, silica gel, ODS, Sephadex LH-20 gel column chromatography and preparative high performance liquid chromatography. Their structures were identified by analysis of physicochemical properties and spectral data, and determined as axillarin-7-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside (1), orientin (2), apigenin-6-C-β-D-glucopyranosyl-8-C-β-L-arabinopyranoside (3), apigenin-6-C-β-D-galactopyranosyl-8-C-β-L-arabinopyranoside (4), apigenin-6-C-β-L-arabinopyranosyl-8-C-β-D-glucopyranoside (5), apigenin-6-C-α-L-arabinofuranosyl-8-C-β-D-glucopyranoside (6), quercetin-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (7), apigenin-6-C-α-L-arabinopyranosyl-8-C-β-D-glucopyranoside (8), vicenin-2 (9), patuletin-7-O-β-D-glucopyranoside (10), luteolin-6-C-glucopyranoside (11), vitexin (12), kaempferol-3-O-β-galactopyranosyl-(1→2)-β-glucopyranoside (13), quercetin-7-O-β-D-glucopyranoside (14), patuletin-3-O-β-D-glucopyranoside (15), 7-O-methyl-quercetagetin-6-O-β-D-glucopyranoside (16), quercetin-3-O-β-D-glucopyranoside (17), nepitrin (18), rutin (19), kaempferol-3-O-β-sophoroside (20), and patuletin-3-O-rutinoside (21). Compound 1 is a new compound, compounds 2, 4, 6, 7, 10, 11, 13, 15, 16, 18, 20 and 21 are isolated from A. annua for the first time. In the anti-inflammatory assay, compound 1 inhibited the release of IL-6 from LPS-induced RAW264.7 cells to significantly degrees with the high (100 μmol·L-1), medium (50 μmol·L-1), low (25 μmol·L-1) concentration.

Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

Erratum: Author correction to "The FAPα-activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway" Acta Pharm Sin B 12 (2022) 1288-1304

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

Inhibitory effect of astaxanthin on oxidative stress damage in lens epithelial cells and its mechanism / 中华实验眼科杂志

Objective:To investigate the regulatory effect of astaxanthin on oxidative stress injury induced by hydrogen peroxide (H 2O 2) in lens epithelial cells and its possible mechanism. Methods:The HLEB-3 cells were cultured with different concentrations (0, 50, 100, 200, 500, 750 μmol/L) of H 2O 2.The cell inhibition rate was detected by the methyl thiazolyl tetrazolium (MTT) method, and the 50%inhibiting concentration (IC50) was calculated.HLEB-3 cells were cultured with different concentrations (0, 5, 10, 20, 50 μmol/L) of astaxanthin.The cell survival rate was detected by the MTT method.HLEB-3 cells were divided into four groups for 24-hour culture, namely normal control group cultured with complete medium, oxidative stress group cultured with 250 μmol/L H 2O 2, 10 μmol/L astaxanthin group cultured with 10 μmol/L astaxanthin and 250 μmol/L H 2O 2, and 20 μmol/L astaxanthin group cultured with 20 μmol/L astaxanthin and 250 μmol/L H 2O 2.The cell apoptosis rate was determined by flow cytometry.The nitric oxide (NO) concentration, superoxide dismutase (SOD) activity, glutathione (GSH) activity and malondialdehyde (MDA) content were detected by ELISA.The protein expressions of nuclear factor erythroid-2 related factor 2 (Nrf2) in nuclei, cytoplasmic Nrf2, heme oxygenase-1 (HO-1) and NAD (P) H, quinine oxidoreductase 1 (NQO1) were detected by Western bolt.The cells were divided into four groups, namely normal control-small interfering RNA (NC-siRNA) group, Nrf2-siRNA group, NC-siRNA+ astaxanthin group and Nrf2-siRNA+ astaxanthin group.The cells were transfected with NC-siRNA or Nrf2-siRNA accordingly.The cells were co-cultured for 24 hours with 0/10 μmol/L astaxanthin and 250 μmol/L H 2O 2 24 hours after transfection, respectively.The cell apoptosis rate was determined by flow cytometry.The NO concentration, SOD activity, GSH activity and MDA content were detected by ELISA. Results:With the increase of H 2O 2 concentration, the inhibition rate of HLEB-3 cells increased.There were significant differences in the inhibition rate of HLEB-3 cells treated with different concentrations of H 2O 2 ( F=12.358, P<0.05). The IC50 value of H 2O 2 on HLEB-3 cells was 264.20 μmol/L.The survival rates of HLEB-3 cells treated with 0, 5, 10, 20 and 50 μmol/L astaxanthin were (100.00±0.00)%, (102.20±1.34)%, (109.50±3.60)%, (115.40±4.13)%, (93.60±2.59)%, respectively.Then 10 μmol/L and 20 μmol/L were chosen as the experimental dose.The cell apoptosis rate of oxidative stress group was (38.50±2.38)%, which was higher than (9.20±0.24)% of normal control group, with a statistically significant difference ( P<0.05). The cell apoptosis rate of 10 μmol/L astaxanthin group was (27.60±4.33)%, which was lower than (38.50±2.38)% of oxidative stress group, but higher than (14.90±1.23)% of 20 μmol/L astaxanthin group and (9.20±0.24)% of normal control group, showing statistically significant differences (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in oxidative stress group than in normal control group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and the differences were statistically significant (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in 10 μmol/L astaxanthin group than in normal control group and 20 μmol/L astaxanthin groups, and the differences were statistically significant (all at P<0.05). There were significant differences in the relative expression levels of nuclear Nrf2, cytoplasmic Nrf2, HO-1 and NQO1 proteins among normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group ( F=43.512, 20.381, 31.014, 23.435; all at P<0.001). The relative expression of nuclear Nrf2 protein gradually decreased, and the relative expression of nuclear Nrf2, HO-1 and NQO1 proteins increased gradually in normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and there were significant differences when compared in pairs (all at P<0.05). The apoptosis rates of Nrf2-siRNA group and Nrf2-siRNA+ astaxanthin group were higher than those of NC-siRNA group and NC-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). The cell apoptosis rate was higher in NC-siRNA group than in NC-siRNA+ astaxanthin group, showing a statistically significant difference ( P<0.05). There was no significant difference in the apoptosis rate between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group ( P>0.05). The NO and MDA concentrations were higher and the SOD and GSH activities were lower in Nrf2-siRNA group than in the NC-siRNA group, with statistically significant differences (all at P<0.05). The NO and MDA concentrations were lower and the SOD and GSH activities were higher in NC-siRNA+ astaxanthin group than in NC-siRNA group and Nrf2-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). There was no significant difference in NO and MDA concentrations or the SOD and GSH activities between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group (all at P>0.05). Conclusions:Astaxanthin enhances the resistance of lens epithelial cells to H 2O 2-induced oxidative stress damage, which may be achieved by activating the Nrf2-related signaling pathway.

Efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors of gastric cardia and fundus: a multicenter study / 中华消化外科杂志

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

Effects of FasL inhibitors on corneal apoptosis and Treg after corneal transplantation in rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of intravitreal injection FasL inhibitors on corneal apoptosis, Fas, FasL expression, Treg numbers in blood and lymph nodes and rejection index in rats after corneal transplantation.METHODS:A total of 24 SD rats(24 eyes)who received penetrating keratoplasty were randomly divided into two groups: PBS group received intravitreal injection of PBS(12 rats, 12 eyes)and FasL inhibitor group(12 rats, 12 eyes). Rejection index was recorded every week and blood samples and lymph node were collected at 1, 3 and 5wk after surgery to analyze the proportions of Treg. Corneal tissue was collected for detecting the expression of Fas and FasL and number of apoptosis.RESULTS: The expression of Fas, FasL in FasL inhibitor group decreased significantly compared with the PBS group(all P&#x003C;0.05); Corneal cell apoptosis significantly decreased in FasL inhibitor group, and it was the lowest at 5wk after surgery; Treg numbers in blood and lymph nodes significantly increased in FasL inhibitor group at 3wk after surgery(all P&#x003C;0.05); rejection index of corneal transplantation in the FasL inhibitor group was significantly lower than that of PBS group(all P&#x003C;0.05).CONCLUSION:Intravitreal injection of FasL inhibitors after corneal transplantation could reduce the apoptosis in all layers of cornea, increase the number of Tregs in blood and lymph nodes, and alleviate rejection.

Sleep status and influencing factors among higher vocational college students / 四川精神卫生

BackgroundSleep disorder can adversely affect human physical and mental health， with important implications for socioeconomic development. And higher vocational college students are subject to various pressures and stimuli exerted by academic studies， job seeking and family socioeconomic status， which may contribute to the onset insomnia symptom or sleep disorder. ObjectiveTo discuss the sleep status and influencing factors among higher vocational college students， and to provide references for improving their sleep status. MethodsIn January and February， 2022， a stratified random sampling method was utilized to enroll 3 300 students from five higher vocational colleges in Wenjiang district of Chengdu city. All the participants were assessed using Insomnia Severity Index （ISI）， Patient Health Questionnaire Depression Scale-9 item （PHQ-9） and Generalized Anxiety Disorder Scale-7 （GAD-7）. Pearson correlation analysis was conducted to test the correlation of ISI with PHQ-9 and GAD-7 scores， and the Logistic regression analysis was performed to identify the influencing factors of insomnia symptom in higher vocational college students. ResultInsomnia symptom was detected in 81.90% （2 497 / 3 300） of higher vocational college students. The detection rate of insomnia symptom among vocational college students yielded statistical difference in terms of gender， family socioeconomic status， being an only child or having siblings， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom （χ2=21.032， 22.172， 8.983， 75.939， 36.781， 32.350， 54.512， 86.561， P<0.01 or 0.05）. Among higher vocational college students， ISI score was positively correlated with GAD-7 and PHQ-9 scores （r=0.620， 0.714， P<0.01）， and GAD-7 score was positively correlated with PHQ-9 score （r=0.824， P<0.01）. Gender， family socioeconomic status， degree of psychological pressure exerted by academic studies or job seeking， amount of hours spent on Internet per day， frequency of physical exercise， and the presence or absence of anxiety symptom and depression symptom were effective factors in predicting the insomnia symptom in higher vocational college students （P<0.01 or 0.05）. ConclusionFemale gender， average and below average family socioeconomic status， moderate-to-severe degree of psychological pressure exerted by academic studies or job seeking， spending 2~5 h， 5~7 h or >7 h on Internet per day， inadequate physical exercise and presence of depressive symptom are the risk factors for insomnia symptom in higher vocational college students.［Funded by Sichuan Provincial Primary Health Development Research Center in 2022， North Sichuan Medical College （number， SWFZ22-C-89）］